Why do we sleep? Well, most sleep researchers are losing sleep trying to find that out as well right now! It appears to be an elusive target. What we do know , is that when you don’t sleep a lot of bad things happen. Disease propagation is one and psychosis and eventual death are others. Most people don’t realize that lack of sleep is deadly for humans, but it clearly is. Sleep appears to most to be a restorative physiologic process. That is what they say now; I am not so sure about this as yet. If sleep is restorative, as they say, what are its targets? We have no idea what the targets really are as of now. What we do know about sleep is that it is incredibly important biologically because every animal has biologic sleep requirements. It seems evolution has strongly naturally selected sleep as a trait throughout all life systems. Since the real answer remains elusive, let’s talk about some things we do observe about sleep. Sleep effects every aspect of human physiology that we currently study. Stem cells, immune function, metabolism, energy biogenesis, cognition, learning and memory for example. It also is intimately tied to metabolism and tocell cycle function.

For evolution to work, a cell first must adapt to its environment. So the first thing a cell would see in an earth day is a period of day and night. It also has to eat to make energy and it also has to control its own cellular division. So in essence the circadian cycle has to “yoke” to the metabolic cycle and its growth cycle. Evolution apparently agreed with that assessment because we now know it to be true. When it is night time, the cell becomes more reduced chemically and electrically. (A lower redox state like we saw in the mitochondrial series). During a low redox time, cells are usually recycling their components using autophagy. During the day while energy is being made to explore the environment, the cell is more oxidized because of increased leakiness of the mitochondria. Another interesting coupling occurs between the circadian cycle with the cell cycle. They are linked via the PER 1 and PER 2 genes. PER 2 directly effects the cell cycle in mitosis. Mitosis is the phase in the cell that occurs just before cell division to generate an offspring. The mammalian period 2 gene plays a key role in tumor growth in mice; mice with a mPER2 knockout show a significant increase in tumor development and a significant decrease in apoptosis (levee 19). This is thought to be caused by mPER2 circadian deregulation of common tumor suppression and cell cycle regulation genes, such as Cyclin D1, Cyclin A, Mdm-2, and Gadd45Î±, as well as the transcription factor c-myc, which is directly controlled by circadian regulators through E box-mediated reactions. This means that sleep is tied directly into to cell cycle functioning and directly into cell mediated immunity at some level. It appears that sleep directly effects the chronic diseases of aging and likely plays a role in cancer development.

Our sleep has characteristics that allow us to study it. Sleep is broken into (rapid eye movement)REM and (non rapid eye movements) NREM patterns. The NREM pattern has three Stages denoted N1, N2, N3. Very little dreaming occurs in any of these stages. N1 stage is characterized by the transition of alpha waves to theta waves on an EEG. This is the stage of a drowsy sleep. N2 is a stage where we see sleep spindles and K- complexes. This stage makes up 45-55% of our total sleep. N3 is deep sleep characterized by delta waves. This is the stage where we see sleepwalking, enuresis, night terrors and parasomnias to occur. REM sleep accounts for about 25% of our sleep in adult humans. This is where we dream. It is characterized by a low voltage EEG pattern and paralysis. I guess a general paralysis during REM makes sense in case we decided to act out our dreams as they vividly occur!

Our patterns and depth of sleep decline as we age. As we age, our sleep declines in duration and effectiveness too. As we age, our immune system and cellular metabolism also appear to decline in concert. This is why as we age we gain more fat over muscle and why we face diseases of aging at a more rapid rate. Remember these cycles are all yoked together. Babies sleep 18 hours a day while a supercentenarian sleeps around six hours a night. This is known as sleep degradation. What if we were able to restore sleep in an older person? Could that effect aging and degeneration? I think the answer is firmly yes. I think sleep hold the potential to a lot of human optimization. And that is why sleep has its own levee in the QUILT (levee 28). The reason it is not higher is because we know so little about how it integrates function into metabolism and in the cell cycle. We also know from meta analysis studies on sleep that sleeping too long or too short affects our longevity. If we sleep below 5.5 hours or longer than 9.5 hours consistently we tend to live a short life with disease. Ideal human sleep is around 7.5 hours a night. We certainly will be exploring why this is the case.

My current belief about sleep is a bit more radical. Think about this for a minute. Did we evolve sleep? Or did we evolve wakefulness? I think sleep is the primordial condition. Think about it for a minute. There is some logic to it. Evolution is based upon finding an environmental niche and exploiting it. A behavior is then naturally selected for according to Darwinian theory. To be active requires wakefulness. In an evolutionary mindset maybe sleep is where we all start and evolution selected us to evolve wakefulness so we could explore our environment. After all, at the dawn of life what did an organism need to do? Think about it. What am I? What do I need to be and how do I preserve myself? It needed to have a sense of self and to distinguish itself from the environment. When you are awake in the environment you have to adapt to the environment, you change. To monitor that change we need to have homeostatic pathways to keep you rooted so that you know exactly what you are up to! When we sleep we cannot evolve to our environment; but, when we are awake, we can perceive changes to our environment. I think wakefulness is a prerequisite for evolution and I think sleep is our primordial condition. This levee is going to be a fun one to explore.

212 Comments

i LOVED this post. i have don't a bunch of reading about pregnenolone in the past after i read some of Ray Peat's stuff and ALMOST started supplementing it with vitamin D- now reading this i think maybe i should have.

Nice to see science catching up to my madness in print huh? Leptin should be the chemical that is light controlled by the central retinal pathways between the retina and the hypothalamus which entangles the molecule to photons to connect between the neuroendocrine and immune systems in the brain to control thermodynamics of the organism. This master photonic hormone acts in the brain as an energy homeostasis regulating factor that triggers a decrease in food intake and an increase in energy consumption by inducing anorexigenic factors and suppressing orexigenic factors by inducing size and shape changes of other photonic hormones in the brain during day and night cycles in a complicated quantum dance. Its own synthesis is mainly regulated by food intake. Food is formed by photosynthesis UNDER THE CONTROL of the sun rays everywhere on Earth. This means food takes its directlive from the sun’s specific frequencies which is contrary to the food paradigms viewpoints today. Since leptin is responsive to food it implies it really pays deep attention to spectral frequencies from light in the human environment to alter growth metabolism body wide. This effect causes eating-related hormones dynamism diurnally and seasonally, but also depends on energy status created locally by mitochondrial flux. Leptin also controls fecundity by controlling the sex hormone cascade because leptin synthesis can be suppressed by testosterone and increased by estrogen and progesterone due to a changing light environment. Now you can see science is no longer blinded by the food paradigm……….they are waking up to a new world order. http://sci-hub.cc/10.1111/aen.12264/

Beth maybe based upon today's standards……but I am talking about our biologic standards. Most people reading this are coming to the understanding from their own perception of what fat really is. Leptin became biologically important from an evolutionary standpoint because food was scarce more often then not and most humans had to protect against low leptin levels not high one like we see today. The paradox in this system and why people get confused is that ultra low leptin and ultra high leptin biochemically cause high US CRPs and this shuts down the thyroid. It is protective in food shortage for survival and it kills you with chronic excess due to chronic elevations of cortisol and insulin simultaneously present in the cellular terroir (levee one). This induces mRNA at the DNA level that up-regulates genes that no longer allow p53 gene to protect our genome from oncogenesis. (levee 16)

There's that "context" word again, I'm realizing just how important it is. If we want to talk about what is optimal for longevity then we must compare things in the context of longevity, and that would be optimal CRP levels. Inflammation seems to mess with everything, definitely DNA repair, so we will have to look at how things work in the case of optimal levels of inflammation. It does seem a bit simplistic that mTOR activation should = Short telomeres and that's that, telomerase is probably more important. What is crystal clear is that there are many factors than influence telomere length strongly and have nothing to do with protein, yet protein helps us be as vital as possible as long as everything is in working order. I think I'm probably going to do 30% protein, 2/3s of that as meat and 1/3 as gelatin, even if protein isn't a problem I think it is still probably a good idea to get some of both gelatin and muscle.

I told you sooner or later I would reveal why Rosedale and I see it differently. He is caught in the quagmire of the research science and not understanding how it translates to a biologic system. This is why Levee one is revolutionary. Doctors must begin to understand that it is not about macro or micro factors…..its about what surrounds the cells over time that determines ultimate fates. Ill give you a perfect example Stabby. the supercentenary group out of Albert Einstein Medical Center in NYC just released some genetic data on their group. Guess what they found. These people had expression of just about every bad oncogene and bad gene we could imagine, yet lived to over 100 years old. Why? What is expressed does not matter as long as there is no traction for it to gain hold. Think of it like this. Our DNA is a stick of dynamite but if you never light it will it ever hurt you? HS CRP is the proxy for the match. Got it? Levee one is so simple but the change in perception brings all these crazy findings into some logical balance now. Discovery is a process that allows us to see something known in a new light…..to gain greater meaning. This is what I discovered when I read about my own injury and it changed my practice. Now I want to change the system of delivery. Just that one thought changes everything.

Question: Pregnenolone steal, could this also happen with a natural Progesterone cream if the supplementer were in this stressed state? I have my suspicions, but you could lay them to rest.

Also, maybe I am alone in this, but perhaps a tool on your sidebar with a list of recommended blood/saliva tests, your take on what range is optimal, and which would be covered in a standard workup (with an asterisk or something?)

This blog is really something you should be proud of! Thanks for sharing.

@ Meredith If your cortisol was sky high yes you need to adjust the dose of progesterone creams. This is why testing must be done by a healthcare professional. The key point I will make here is the more you test the more control you have over what is really going on. You just must make sure your doctor is on board with you. These days there are physicians who will help you. Meredith the site is not about offering medical advice for individuals. It is about explaining why something is happening or why it is not. We can lead you to the answer and then its your choice what to do with that thought. I want to give you control back for your health.

@Harry you are looking for a problem in the ratio between the RT3 and the Free T3. i.e dividing the Free T3 by the Reverse T3 (Free T3 Ã· RT3). For healthy amounts of RT3, The ratio result should be 20 or larger. If it happens to be lower, then you have an issue. If you use the total T3, you are looking for a ratio greater than 10. If lower, you have an issue. The real problem is that the units that rT3 and T3 are measured in are often different! Why I have no idea but it creates a calculation problem. I usually ask my lab to calculate it for me so I dont have too. Then I give the news to the patient.

Jack I am going to agree with Beth above and dispute your BMI numbers. I am 5' 10", 148 pounds, BMI is 21.2. This is the 7th percentile. To avoid lepton resistance I need to lose 9 more pounds? That would put me under the 2nd percentile. Perhaps a discussion on what a correct BMI should be followed up by your usual excellent research? Is it time to re-write the BMI tables?

John the numbers are guideline. They are not set in stone. Generally when one goes above those BMI numbers we begin to see TNF or HS CRP creep up. That is the sign we need to look for that we are not. There is a bell curve distribution of course for a population. Women tend to have higher leptin levels than men due to increased fat stores for childbirth. But the point should not be lost that the we can track early inflammation as one's BMI evolves. That is why I am a huge believer in body composition testing. Very accurate fat mass measure. BMI is not something I even use any longer. I use body comp scores.

I will often draw a serum ferritin too in women because a low ferritin can cause a high reverse T 3 as well. It is an inhibitor of the conversion of T4 to T3 by the 5' deiodinase enzyme. Most common cause is how HCL acid in the gut. So if I see a patient on a proton pump inhibitor I think about checking a serum ferritin too.

This is my first time i visit here. I found so many entertaining stuff in your blog, especially its discussion. From the tons of comments on your articles, I guess I am not the only one having all the enjoyment here! Keep up the good work.

If low leptin causes high levels of HS CRP much like high leptin, as you mention above, is there a point at which you can have too little body fat, to the point where it is unhealthy? I asked a similar question on PaleoHacks – Leptin, where's the sweet spot?

Maybe I'm missing something? I guess what I'm trying to get at is, What is the connection between body fat levels, leptin levels, and leptin sensitivity? Can one walk around at sub 10% body fat (Im assuming this means low leptin) and still not cause excess inflammation, which would lead to deleterious effects, down regulation other bodily functions, etc.? Or does low body fat not always mean low leptin, if said person is leptin sensitive?

Todd energy balance is what leptin controls. So there are three basic states. Energy deficit (anorexia or starvation) Energy Excess (obesity) energy balance (normal) When you are anorexic or starving TNF ( and so does HS CRP) goes up. This causes leptin resistance with low leptin levels at the receptor. The high TNF completely wont allow leptin into the brain at all. So the brain is blind to energy status. So it shuts off the thyroid to survive until it does know what is up. Shutting off the thyroid stops conversion of T4 to T3 and the remainder shunts to rT3. This keeps the thyroid and muscles on lock down from burning any fat no matter what. It does this as a protective mechanism. This is actually why leptin evolved. It really was protective. Today we see the other end most commonly in obesity. Where high levels of leptin shut signaling down. The one thing that is the same is that inflammatory cytokines control the leptin signal in all cases. That makes the leptin receptor is pleiotrophic. It means it can act give multiple results to multiple inputs based upon what other parameters are present in the human. Many other pathways in the body work this same way. Its a key concept that you must get. Because when we get to mTOR and AMPK your head will spin. They act sometimes in six dimension to many many chemicals and then can have different results from the same pathway.

WOW…I actually understood this Jack! So the stress I was under with mom's illness lead probably to the cortisol issue, I had lost 58lbs last spring into fall until she got sick.From Nov. to Feb. I was gaining again, I get the stress.I am so excited right now you just don't know, thanks for giving this info to me even the boys are syked! This is do-able. I wish we knew this when I was a teen, maybe life could have been different for our family! I sure hope people listen to this in 11 days I have lost 11lbs. I am amazed. To bad the medical association doesnt get on board so many people like me can change their future and its not hard at all. Got a cure for my smoking because this is a real challange for me. I have tried so hard in the past 3 months with no effect!

What are your thoughts on problems with LOW cortisol? Do you see much of this in your practice? I've been dealing with this issue for a couple of years and am now taking replacement cortisol along with thyroid medication, specifically a T3 only med due to high rT3 levels. I'm really intrigued here.

Yes i do…..the most common people who have this problem are people who overtrain and people who eat a large amount of omega six FFA. If you eat alot of processed foods we see it too. There are some people with end stage type two diabetes, and end stage fibromyalgia that have this too. People with serious gut issues also can have this because of the chronicity of their disease wears the adrenal glands out. A salivary cortisol test is pretty diagnostic and then you treat it. But you have to know about it first if youre the treating doc. Cancer patients also get this problem.

Jack, thanks so much for the info. Is serum HS-CRP reliable? Isn't it known to be episodic? For example, I'm a T2 diabetic w/insulin resistance and 2 autoimmune diseases. Yet my CRP is usually at 0.3 (the lowest detectable) and my Westgren Sed Rate is always at 1 (minimum next to 0). I'm 5-10/160 eating Paleo and in good shape. CRP was elevated (3.5) only once and that's becuz it probably coincided w/my gout attack.

Natty now you know why your thyroid test are normal. You need to become leptin sensitive are rule one. I use HS CRP and think its pretty accurate. I also bet your vitamin D is sub 30. You need to get aggressive with this. If not you will never eradicate your diabetes. And you can do just that. A regular CRP is not the same test as a highly sensitive CRP. They are two different tests…..be very aware of that.

Chronic low-grade inflammation is a feature of obesity and is postulated to be causal in the development of insulin resistance and type 2 diabetes. The aim of this study was to assess whether overfeeding induces peripheral insulin resistance in lean and overweight humans, and, if so, whether it is associated with increased systemic and adipose tissue inflammation.

Subjects gained 2.7 +/- 1.6 kg (P < 0.001) and increased fat mass by 1.1 +/- 1.6% (P < 0.001). Insulin sensitivity decreased by 11% from 54.6 +/- 18.7 to 48.9 +/- 15.7 micromol/(kg of FFM)/min (P = 0.01). There was a significant increase in circulating C-reactive protein (P = 0.002) and monocyte chemoattractant protein-1 (P = 0.01), but no change in interleukin-6 and intercellular adhesion molecule-1. There were no changes in fat cell size, the number of adipose tissue macrophages or T-cells, or inflammatory gene expression and no change in circulating immune cell number or expression of their surface activation markers after overfeeding.

CONCLUSIONS:

Weight gain-induced insulin resistance was observed in the absence of a significant inflammatory state, suggesting that inflammation in subcutaneous adipose tissue occurs subsequent to peripheral insulin resistance in humans

they claim there was no rise in inflammation, but the creactive protein went up, there was no change in fat cells and no immunity change. still inducing insulin resistance or did the study induce leptin resistance and a longer term would have induced more problems?

I would not assume at 28 days of over feeding causes leptin resistance. But they did have higher levels of CRP which is consistent with my clinical findings that TNF is the first sign of leptin resistance. The easiest way to measure it clinically is the HS CRP. That is why I do it. We don't know that they are leptin resistant because they never even assessed it.

This is my first time i visit here. I found so many entertaining stuff in your blog, especially its discussion. From the tons of comments on your articles, I guess I am not the only one having all the enjoyment here! Keep up the good work.

Not only are we generally getting insufficient UVB exposure so vitamin D3 25(OH)D levels are lower than optimum, the lack of outdoor bright light exposure during the day, combined with too much bright light during the evening and light pollution at night, leads to disruption of circadian rhythm and insufficient production of melatonin. Both melatonin and vitamin D3 are both fat soluble anti inflammatory anti oxidants and our ability to synthesise both declines as we age.

Ted thank you for your comment. Melatonin has huge effects centrally in the brain and prior to 1925 I think it played a much larger role in metabolism. Artificial light became common to human existence in Paris in 1925. Its effect on vitamin D is well known especially in airline pilots, astronauts, and truck drivers. Ted I really appreciate you posting this. You definitely jumped ahead in the story but I promise you the quilt will get to the central effects of hormones because they are critical. I would also say to you the use of progesterone has amazing effects on cortisol and even is able to stimulate neurogenesis in the CNS by effecting cortisol production and leakiness of the mitochondria or long lived neurons to effect mitochondrial biogenesis. There is much more to the clinical effects of vitamin D3 than clinical medicine appreciates now. The research findings has far surpassed current clinical recommendations for disease prevention. When I get to the immunity levee vitamin D will be playing a starring role.

Dr. K wrote: "I will often draw a serum ferritin too in women because a low ferritin can cause a high reverse T 3 as well. It is an inhibitor of the conversion of T4 to T3 by the 5â€&sup2; deiodinase enzyme. Most common cause is how HCL acid in the gut. So if I see a patient on a proton pump inhibitor I think about checking a serum ferritin too."

i am 46. Low ferritin can also be caused by excessive menstrual bleeding, which i have. my ferritin stores are less than 1, even though my hemoglobin is 13. i'm guessing that my heavy flow is caused by fibroids. if my hemoglobin is 13, do i really need to worry about low ferritin? what ferritin level should i shoot for? i supplement with iron, but sporadically and probably at too low a level. i got my hemoglobin up from 9 (i believe) by taking aleve the first 3 days of my period, which cut down on my flow substantially. also, since fibroids and concomitant heavy bleeding are the number one motivating factors for hysterectomies, could you please do a post on fibroids? what is the safest procedure to have them removed, or is it best to try to manage them by a paleo diet, cutting down on flow with aleve, and iron supplementation? i've read that they shrink after menopause, so maybe it is better to manage them rather than do something risky to remove them.

i am asking you about an issue that affects many women. i hope that you can provide some general guidance and am not asking you to give me specific medical advice. thank you so much for sharing your experience. 🙂

@V…..if you have heavy flow you need to look for an underlying hormonal problem causing it. I would strongly recommend you get that looked into. Most fibroids can be dealt with without surgery but you will find it tough to find an OBGYN who is willing to leave your uterus alone and treat you with bioidentical hormones. Women need to mandate they want that option over having their uterus's removed with regularity. Those options are clearly laid out in the OB/GYN bible, Speroff's textbook on OB/GYN. I have never understood why this is not aggressively treated medically.

Tammy there is a lot you can do. The first thing to do is get all your labs done and get salivary cortisol levels done to see truly what your problems are. The way to gain control back Tammy is to quantify yourself with labs. Once you know something is amiss you can help your doctor treat the issues. Your doctor may not know about these tests but there likely is a doctor in your area who does. Start researching it.

Pardon me if I'm being dense, but what does one do, exactly, to get cortisol under control. Some of the steps in regaining leptin sensitivity seemed to indirectly cover that, but are there other steps to control cortisol in and of itself?

@Adriana I have no experience with them at all. I would search the internet and google for reviews on it. @ Brahnamin the treatment for a high cortisol depends upon its cause. If it is obesity I have already begun to lay how to fix it. LR leads to hypercortisolism. Fix the obesity and it goes away. If it is induced by other means we have other options. I will reveal more about cortisol as the Quilt unfolds.

Dr. Kruse – I've met many 40-something males with 'metabolic syndrome' who are treated by the symptoms, ie. meds for bp, cholesterol, high trigs, hypothyroid. Once they take control and lose weight, get their leptin reset and become healthy, they usually get off all their meds–except hypothyroid meds. Conventional wisdom is that the thyroid will always need Synthroid or similar. Is there a protocol for stopping hypothyroid medication after the 'metabolic syndrome' symptoms disappear?

@Tim. There are two possibilities I have seen. In morbidly obese there is permanent damage to the hypocretin neurons in the hypothalamus. This can lead to life long issues that will need treatment after the weight is lost. Not as common in my practice. More common is after two years of regaining leptin sensitivity the body adapts and balance occurs. The biggest issue hormone wise in men in women is the sex steroid hormones which are dramatically altered and often need to be augmented for a period. This is also true of vitamin D levels. But they all seem to come back to a baseline within two years of healthy living. Hope this helps.

Thanks! I won't beat this to death…It sounds like the thyroid will be OK once everything is in balance. Is there any harm that could come from continued (unneeded) Synthroid therapy? What would be the best test to see if Synthroid could be safely stopped?

Jack,,,i love ur site,,,i would like to ask u a question,,,i am 57, already went through menopause,,,my dr changed my thyroid med from synthyroid to armour thyroid and i have been doing low carb hign fat for about 3 months,,is there anyway that this could have caused me to start bleeding,,,been on provera 2 a day for 10 days….but still bleeding,,,i would appreciate ur imput,,,,my dr will start saying histerectamey,,,i have had throid and hormone trouble for 30 years thanks 4 all u do,,,and for telling it like it is,,,God bless you and yours,,,,thanks regina

@ Regina Provera? Yikes. I dont advocate any synthetic hormones. They cause major issues. Why not dump Provera and go bioidentical with prometrium? And before you have your uterus removed go see an OB/GYN that uses bioidenticals and wont try to take your uterus out right away. Most hysterectomies can be avoided with good old fashion BHRT. You need to read some of Suzanne Sommers books on this issue because she has done a good job explaining this issue.

Dr. Kruse, I'm learning so much! Thank you! One question: You said you tackle the CRP first? Did you mean you watch for it to go down first (of all measures) with a healthy paleo diet? Or do you tackle it in other ways as well?

Thanks for your quick response! It wasn't HS CRP but the "cardio CRP" was at 14.5 last time. Scared me silly! I've lost 40 lb since November and have been eating 90% Primal for about 3 months in an attempt to just "maintain" for a while before losing "with intention" again. Was surprised to find myself actually losing as long as I stuck to Paleo without dairy… Now I understand why! I'm going 100% Paleo after reading your blog. I've been eating lots of Salmon and taking Omega 3 until I ran out a few days ago. Unfortunately, it was bound with soy oil, and I know soy isn't good for me. I hope I can presume plain old fashioned Norwegian Cod Liver Oil would be RX grade?

HS CRP = cardiac CRP just so you know. They are the same protein. 14.5 is off the charts. above three I get antsy. you are almost five times that level. I would recommend going to consumerlabs.com to get Rx info on Fish oil. I am a big fan of LEF.org supplements.

Thanks again for your quick response. I was surprised my doctor didn't react as you and I did on that number. Since I had to request that test to begin with, I suspect she just isn't knowledgable about it and needs more education, as you know many doctors do. At the time of that test I did have extensive hip pain (inflamation), somewhat better now. We surmised that had a definite impact on the CRP. And haven't had the tests redone since I've lost some weight.

Ah it might be. 🙁 I have celiac disease too. And my C-Reactive Protein has been high a long time. Homocysteine levels too though they have fallen quite a bit since I've lost weight. I will keep following this though. You are a genius! I've been telling lots of people about your blog.

Can I just say what a relief to find someone who actually knows what theyre talking about on the internet. You definitely know how to bring an issue to light and make it important. More people need to read this and understand this side of the story. I cant believe youre not more popular because you definitely have the gift.

I've been on the paleo life style for over two years. Lost some weight but seemed to be plateaued at a 38" waist. I have had a recurring problem with gout flare ups every three months or so and take prednisone for relief. I don't eat fruit, but it seems that I can't eliminate enough uric acid thru my kidneys. A while ago I read on the perfect health diet web site that eating a 50gram of starchy carbs will help the body process this extra uric acid. It seemed to work for more than 6 months , after reading your site I have started eating breakfast every morning as you suggest but now I am now having another flare up. Do you have any thoughts on this subject and why it affects only a small % of people on a paleo diet? The medical people I have seen are clueless as to what's going on. Thanks for helping us understand the science behind a healthy life style.

Thx for this great info, Doc. This past Dec I got a wake up call when my A1c went above 6.5 I started eating Paleo and took myself of statins. Eating btwn 20-30 gm net carbs per day, about 85-120 gm protein, and 45-75 gm fat (mostly low O6 fats – occasionally binge on nut butters) I've been doing great -Lost about 50 lbs so far (30 more to go), feeling better than I've felt in years – for the most part, I'm not hungry and have to force myself to eat 1000 cals per day, no more achy knees, allergies much better, more energy overall. I had a check up again this week and overall things looked good in bloodwork. Triglycerides down from 81 w/statins to 62 w/o. HDL up from 55 to 66, LDL went up from 61 – 107 (which I expected given that statins lower LDL) Doc did not do LDL subtypes but I presume my LDL is the "fluffy" type and that low triglycerides shows that I've been truly low carb. Anyhow, my surprise was this – My A1c went down to 5.7 which is considered normal – but it's not nearly as low as I expected given that I'm only eating 20-30 net gm carbs per day.

I'm wondering if I could be Leptin resistant and if this accounts for the still somewhat high A1c value? One thing I've noticed that I do that's different from your leptin reset protocol is that I'm usually not at all hungry until around 11 am. I'll eat a large salad w/protein and then around 7pm I'll eat dinner. Usually no snacks in between, tho occasionally I'll have some protein late afternoon. Why is eating high protein first thing in the morning so critical?

@bean. HbA1c is a measure of glycation of RBC’s which have a lifespan of 120 days. So HbA1c falls slowly over time. The key to follow is your trend. You want it to go even below 5. I would strongly recommend asking your doc to also get fasting insulin levels too. You want that level below 2. If your labs both show those numbers you can bet your leptin status is solid. No way of knowing for sure without your labs, weight, BF% etc…..glad you enjoyed the post.

@Jack S I am not a fan of just saying eat more carbs as Paul J does. I think if your uric acid levels are high you are not drinking enough water and you might want to increase specific fruits…..like cherries or cherry extract whose flavinoids really help clear uric acid from the body.

Getting in to see your doctor and getting a complete set of labs done is where I recommend all people serious about regaining their health begin. It requires that the doc understand what and how to interpret the data. Not everyone is comfortable doing this. I suggest finding docs in your area who do this routinely. Many of the pcps around me are doing these things. Everyone has a special expertise in this. One day I may list the tests I use……but it is useless when you have no one to make sense of the data. That is why I have resisted doing so on the blog.

I would also suggest anyone who is interested in seeing how a leptin reset works for people who have never physically seen me but took my advice do with minimal guidance take a peak at the thread at marks daily apple in the nutrition forum that is now close to 370 pages long. I think this might open some of your eyes on how this advice plays out clinically.

Hi I'm new to your site and ideas and just trying to learn. The hard part is I think I have an unusual history. Severe asthma with equally severe IR and HPA axis suppression. Thanks to 15 years of oral steroids before the advent of Advair.

This last suppression episode lasted for 15 months (mostly due to medical mismanagement). When I was insufficient, it was very easy to lose weight. I could eat sugar and still lose (which was soooo different from the usual IR weight gain mode my body is in).

When the switch flipped and the HPA axis came online, until I got off steroids, I could not lose weight no matter what I did. So I definitely have personal evidence that high cortisol is no good for weight.

The thing is, even off oral steroids (still do inhaled with spacer) I seem to be struggling. I lost an initial 9lbs and now nothing for 2 months. Previous stall was 7 months. Need to lose another 30 lbs or so.

I will be tweaking my diet a la your suggestions here, but I wondered if, since a lot of my situation is externally applied via oral steroids, there was any other advice you might impart? Any books I should read on leptin or inflammation (I've read both Taubes and Mark's books, but need to learn more).

The other thing I've noticed is that weight loss triggers the asthma. Each time I've had the initial LC rapid weight loss, I ended up in the hospital. I'm the only person I know whose health doesn't change with LC. I'm sicker, but skinnier. Even my messed up cholesterol stubbornly stays the same. I think I need something more than low carb, but I don't know what that is.

There really are no great books on leptin. The story on it is being written as we speak. I think you need to read as much as you can on it in the literature. You could start with Mastering Leptin by Byron Richards and use his bibliography in the back of the book. It links a ton of seminal papers but the latest stuff coming out now is no where in printed book.

I'm sitting here bawling lol! I'm on 5 of those meds and different serotonin inhancers yes plural. I'm still having to take the omeperazole every couple of days the acid reflux is really bad. The Beyond HCL isn't enough YET. My doctor had to take me off the Cephalexin today it just made me way too nauseous and week. I'm hoping the cellulitis is good and dead!

Jack idk what you like to be called but I'm hell bent on getting healthy! I thank my HP that I found your site and MDA I'm almost done with Mastering Leptin and next is Primal Blueprint!

Thank you soooo much!!! I'm one that will probably have to take thyroid replacement but if I can quit being, as my husband calls me, the walking pharmacy I'll be thrilled!!!

I have adrenal fatigue with low cortisol all day. My reverse T3 is very high at 669. My Free T3 is 2.3. My Vitamin D level is 99 because I have taken supplements for a couple of years. My ratio of Free T3 to Reverse T3 is between 3 and 4. I mainly eat eggs, meats, vegetables, nuts, and use coconut oil daily. I also take fish oil daily as well as several other supplements based on my own research. A lot of people recommend hydrocortisone for the adrenal fatigue. I am scared to do this. I have started on an Adrenal Glandular by Nutricology and licorice. I am also taking kelp for my thyroid. I am tired and depressed most of the time. Will your dietary recommendations help fix my adrenals and my thyroid? Any other suggestions? Sorry for so many questions, but I am desperate!

I live in Alabama – close to Birmingham. Could I become a patient if I traveled to see you? I am having a hard time finding a doctor that I trust. Thanks for your time!

Your problem sounds pretty serious and you may need to consider doing things you might not want to. This will require you and your doctor sitting down and having a serious heart to heart. Your HPA axis may need a jump start with cortisol to get you up and going. I think you need to get your DHEA and sex steroid hormones tested if you have not done so already with your situation. I also think you need to consider a lot more interventions for that problem.

Thanks for your quick response and the link. I had not read it. I have had my DHEA tested, and it was low. My testosterone and progesterone were high due to supplementation (compounded cream). I am currently implementing many of the suggestions in your blog as I have researched adrenal fatigue for at least a couple of years. I am currently looking for a new doctor as I have not been pleased with my improvement under my last doctor's care. I was under her care for over a year and saw minimal improvement. I am afraid that if I go on the cortisol I won't ever be able to get off of it. I am also afraid of weight gain as I have about 10 pounds that I can't get off no matter what I do. I have been taking adderal for several years which I know is bad for my adrenals, but I don't think I could do my job as a school teacher without it. I have gotten off of the adderal twice, but then some family problems caused my adrenals to crash again and I had to go back on the adderal to function.

I have considered a ketogenic diet and possibly the GAPS diet as I have several digestive issues and depression.

@Yxy You know that Cushings can cause significant hypothalamic changes so a full work up would need to be done to see truly where you are now. And since you have had two transsphenoidal approaches this really mandates it. Often the adenomas of ACTH are hard to find and the surgeon has to become really agressive and some normal pituitary is taken out with the tumor.

As for your comment about biochemistry not being the same as when you went to grad school……youre right. What we do know now has changed a bit. Adrenaline (epinephrine) is the acute fight or flight responder but the proper context here is about metabolism and leptin. This is where ACTH and cortisol chronically completely negate adrenaline. Excessive chronic ACTH or cortisol completely shut down the symapthetic nervous system out flow at the brainstem level. So when someone is LR adrenaline is basically useless to the them over time. This is why so many unfit people and the obese rely on stimulants like caffeine and nicotine to get them going. They become dull to its adrenergic effects on all receptors. Surgeons like myself see this all the time in surgical cases where cortisol or ACTH is elevated and even giving the patient levophed (synthetic adrenalin) will not move their blood pressure and have little action on the heart. This is also why nurse refer to levophed as "leave them dead". The reason is that the levophed does not work well on the organs that are under stress but it does clamp down on others that can still respond to its adrenergic effects. So you see clinical medicine must take the cortisol situation into account to see how it will affect the situation. The underlying cortisol issue must be dealt with first. So in essence when a in vivo human has chronically elevated cortisol as one does in LR, cortisol becomes their flight or fight hormone and not epinephrine. And that is a big problem. Remember the point in the article was that context matters. In a fit person who still can respond to adrenalin the context is different. Your comment is based upon the normal physiologic response and my article is based upon what occurs in the pathologic state. I choose not to publish all your comments because I felt many would not understand your point because they don't understand the context problem that you seemed not to grasp. This is why in learning from a book differs from real life clinical medicine.

I would have guessed I'm leptin resistant (which would explain difficulty losing weight by "Standard" methods), but the normal CRP and high calcitriol throw me. Any thoughts on HIGH vitamin D and high BMI?

Love the blog, I'm leaving chem E to pursue a masters in biochemistry.

@Andrea My bet is that you likely do have an underlying hormonal problem. It could be LR or a thyroid issue. I think you definitely need to consider testing to get tot he bottom of it. When you get a thyroid panel make sure you get Rev T3 and TPO Ab panel too. If you can get your salivary cortisol level done too. I bet those will uncover the mystery.

Dr. Kruse. Thanks, I had thyroid panel done in April of this year, T4 8.7, T3 Uptake 30%, Free T4 Index 2.6, TSH 0.88, T3 88.0. I'll check into getting reverse T3, TPO Ab and salivary cortisol. I have a good doc that will write scripts for tests, insurance the more difficult matter.

Question, Dr Kruse, I've been looking and maybe I missed the answer: my thyroid condition was determined to be autoimmune when I was 14 (yep, I was over weight then, 16 yrs ago) and if I follow the instructions on my medication, it says to wait anywhere from 30 min- 1 hr before eating. I am not the same person now, I actually weigh less now than I did then (now: 5'2 & 129.4 lbs), but am curious if I still might be some-what LR. What would you recommend: eat anyway, take the medication later; get LS and hopefully stop taking the medication? I have been on the primal diet, loosely, for about 1 -11/2 yrs and just started over with the Primal Challenge.

Hi Doc, this is a question for men in general: Besides avoiding high carbs/PUFA's and regaining LS, what else can we do to naturally increase testosterone and decrease cortisol? 1. does heavy lifting help? 2. how much would you say is overtraining and there defeating the purpose?

Also, not to sound technical, but if one is 20-30lbs overweight (not morbidly obese or diabetic), what kind of testosterone and cortisol derangements are we talking about? Some effect, or very dramatic effects? Thanks again!

I often get confused with the chicken or the egg effect of cortisol, insulin, leptin, thyroid. I know they are all inter-related somehow, but the chain of events still confuses me sometimes. Can you help?

@Carlos The most common way is Leptin resistance leads to insulin resistance and that ends in adrenal resistance in most cases of obesity……But other ways are possible for other disease processes like arthritis or PTSD.

So how do I lower my corisol? Just with the paleodiet? My urine cortisol is 2.5X normal (and I’m on synthroid and lorazepam…join the club, right!) My endocrinologist is checking for possible issues with my adrenal glands and/or pituitary.

What if someone has been on hydrocortisone for 5-6 years with no end in sight? I still have high RT3 even on a good dose of T3 only med and my blood cortisol still comes back high on a dose of 30mg hc. My doctor basically put me in the addisons category last time I was there. That was the point I basically gave in to the fact that my adrenals may never get better. Now I have found this blog and your website and have a little hope left.

Is there something I need to be looking for while doing the reset as far as thyroid goes? My doctor allows me to adjust my meds according to how I feel and temps. Since the temps may drop as you get better, this confuses me a little.

I had a thyroidectomy in February and have put on 30 lbs. I was thinking of trying the HCG diet but just found your website and am much more impressed by the info you provide. Would any modifications need to be made for someone who no longer has their thyroid? Is it possible to "reset" and get over the maddening sugar cravings even though my body no longer functions the same way. I did not crave sugar before they thyroidectomy and ate a low carb diet out of desire not necessity. Sugar and bread were a treat not a craving.

Thank you so much for replying. I am on thyroid meds (not really any choice.) I am excited about starting this program! It is really fantastic that you provide all of this information in a way even I can understand.

Please tell me your thoughts on using Armour after a total thyroidectomy, as opposed to Synthroid and Cytomel combined. I am on round one of the HCG diet (5 years post TT) and am doing well; many on the Yahoo HCG Group have recommended your blog, so I am reading….fascinated! I just want to know if my situation requires any modification on the path to LS

Still trying to understand all of this. Just did blood work, no reverse T3 (Dr. would not order). What is a high HS CRP? Mine was 2.1. Test claim I am borderline high cholesterol, 209, tri-54, hdl-60, ldl 138. I just lost 38lbs on HHCG. I have been reading your site gathering info. Trying to start into leptin reset. Thanks

Dr. Jack, thank you so much for all your wonderful posts. I'm so glad I stumbled on this site after researching leptin resistance. Like most I've read, I'm overwhelmed by the wealth of information! I'm a closet "scientist" and am just soaking this up. I too have had a thyroidectomy and am on Armour. I have been officially diagnosed with celiac disease, lupus, systemic candida, insulin resistance, adrenal exhaustion, PCOS, fatty liver disease by various doctors over the last few decades. But, I'm not feeling better as quickly as I feel I should be with all the various protocols I've been put on. I've always felt like I'm spinning my wheels going round and round. I'm tired of wasting time! I'm a 54 year old, 60-pound overweight post-menopausal woman who wants to know what it's like to be well. After reading alot here, a light is starting to come on that the candida was my beginning as I was born with thrush. Never felt well as a child and definitely not as an adult obviously with all my issues. I have had an insatiable sugar hunger all my life. So, again, after reading most here, Dr. Jack I'm "hearing" that I need to: a) following your Leptin Rx, b) go paleo, c) follow yours/Robb Wolf's autoimmune elimination protocol to tackle the leaky gut? That the leaky gut correction will be the healthy beginning for me??? Oh, and I think I remember reading somewhere in this website you said to aggressively tackle the candida.

Yup, it's a beasty beast alright! I've tried before to kick it, but I let it creep back. I'm a stress eater. Well, it appears I have my work cut out and I feel I finally have firm resolve to "just do it" after reading your info. Tons of info and tons of science to back it up. THANKS!!! I hope and pray that I'll be back in a few months with a transformation testimony! 🙂

regarding your response to Kathleen and candida… is there a test that can test levels definitively? what if you have become immune to the standard herbals, or the herbals are making your leaky gut more sensitive/leaky? would you do a Rx anti-fungal and continue to follow strict paleo, leptin reset, and a leaky gut healing protocol? i know its a bastard to get rid of, is this your way of saying foggedaboudit? if there is a way can you please suggest? thanks again for all the great articles.

Hi Dr. Kruse. I am back to ask you for your help. I finally got in to a new doctor and had the "optimal" discussion with him. He was very understanding and obviously wants to help, but after looking at my test results, I don't agree with his conclusion that I am "extremely healthy". I am a 40 y/o female taking Armour for hypothyroidism.

Of utmost concern to me is serum glucose – 96 and A1c – 5.4. However, I'll give you the other results as they may help paint a picture:

A/G Ratio 1.3

Globulin 3.2

Creatinine Serum 4.0

Estradiol 24.5

LH 7.0

FSH 9.1

Glucose, Two hour post-prandial 74

Insulin-like Growth factor 172

T3 105

T4, free 0.66

Testosterone serum 25

TSH 2.240

Vit D 31.8

I realize you are very busy, so your consideration is so very much appreciated. Thank you for what you are doing.

Sorry – forgot to add Antithyroglobulin AB – 53, which may be an indicator of hashimoto's? I think there's something in all of this, but I don't know for sure where to start??? Just point me in the right direction please. Paleo diet, supplements, BHRT, etc. I am desperately afraid I am headed for T2D, and there's no preventive help such as what I've read on here. Thank you again,for any help you can give.

For the 1st time, re-reading this, I noticed that ALDOSTERONE is also lowered by pregnenolone steal.

I don't have deficient cortisol, but even my dr told me to start having a tsp of salt in a glass of water every morning, & keep my salt intake high, because my sodium levels are low-normal & I get weak without it…usually right at the bottom of normal despite high salt intake. This let me to wonder if I'm low in aldosterone. I also have to urinate pretty quickly after downing water, and pretty copiously!

Low aldosterone: can't hold salt. Low sodium, can't hold water.

With my high a.m. serum cortisol, I couldn't have addison's. (P.M. was not tested.) Hx of cortisol crashing spontaneously & idiopathically. No dramatic crashes in recent years; maybe bc of eating very low carb.

Yet in researching it, I found that aldosterone deficiency is supposedly very rare. My father & half-sister also crave(d) salt like I do, & dad died of kidney/bladder cancer. (Any connection likely? He was a heavy smoker, tho.)

Is it possible someone with high salt craving (& it does restore me from weakness when I eat it, tho the need is rare now as I salt heavily) could actually have an aldosterone deficiency, not from genes, but from pregnenolone steal?

@Mimidiet it is more common today than it was 30 yrs ago because people are now realizing that pregnenolone steal syndrome is a real problem. I never heard of pregnenolone steal syndrome until 2003. It is very possible this is happening.

I found your site yesterday and cannot pull myself away from it! FASCINATING!!! I am a 42 year old female who has been following Mark's Daily Apple, well, daily for about a year. I lost the weight I wanted going "primal", but continued to be very fatigued, cold, irritable, etc. After NUMEROUS tests, it was discovered my sex hormones were in the toilet and my thyroid was a bit hypo.

Reluctantly, I was put on Estradiol, Prometrium, and Androgel by my Gyno. My Endo has me on (surprise, surprise) Synthroid. I am now ravenous constantly AND have regained ALL the weight I had lost (I still eat/live primally). Yes, I have a bit more energy now, but I have lost significant hair and feel horribly obese (I am not, but I sure feel that way).

I look forward to beginning your Leptin Reset for the next 6-8 weeks. My Gyno says he's happy with my levels of sex hormones now and doesn't want to change anything. I see my Endo tomorrow and am not sure where to go from here. Cytomel with my Synthroid? Armour? Get off it all?

I am assuming it's the thyroid med that's creating this hunger/weight monster, no? Or maybe it is the combo of everything. If you have a recommendation of what I should ask my Endo (and/or direct me to a previous post), I would be sooo appreciative. I truly feel like I'm back to square one.

Thanks for such an informative and helpful site. I wish I could sit in front of my computer and digest this all day!!

Dr. K, I've been doing your Leptin Rx for 4 weeks now. I am a 43-year-old woman, mom of 2, and I've never been overweight by more than 20 lbs. I have been on a low carb high fat mod protein diet, paleo style, for almost 3 years now. I couldn't lose the last 15 lbs of baby weight despite trying every diet. I felt better on low carb high fat paleo, got sick much less often, more energy, and so stuck with it, despite some gains in weight. Finally went on hcg this year and lost that 15 lbs. In the last 4 months since I stopped hcg, I have gained back 10 lbs. I still do the same paleo diet. I haven't had any sugar or starch…no bread, pasta, rice, etc. and no desire for any of it. I gain weight with my mens. cycle each month about 2-3 lbs come on right on day 1 or 2 of my cycle and then, I spend the rest of the month trying to get it off and it's stuck like glue. Sometimes I'll lose 1 lb and then, gain it back. I think my hormones are messed up but my cycles are so perfect, 28 days, not heavy, some PMS but less than I ever had in my 20s. I was told I was estrogen dominant (before I got pregnant with my second) and did the progesterone cream for about 6 months. Other than that, I am under tremendous stress, financial, emotional, grief (major losses in my life), and not much support. I am doing the Leptin Rx even though I'm not 100% sure I am LR since it's only 10 lbs overweight. Something is clearly wrong if I am gaining weight without changing my diet. I eat 70% fat, 20-25% protein, 5-10% carbs. My carbs are often only about 15g for the day. I have been trying to actually increase them to get to 25g. I want to heal myself before I keep gaining and gaining and really have a big problem. Thanks for your insight.

@Claudia after reading this all I dont think you are leptin resistant so the Leptin Reset may not be ideal for you. Hence your outcome. I think you need to follow the Leptin Post Rx written on Nov 16, 2011.

Thanks Dr. K. Should I still continue the reset for 2 more weeks since I've already been doing it for 4 weeks? It has helped me to eat the BAB and not snack (which I definitely always did) and not eat at night (another thing I did before, although not an out of control thing, just a snack every night). My sleeping is also better. I had nightmares frequently at first and many vivid dreams. I thought that was very unusual. Is that typical? I stopped doing so much cardio. Can I go back to some HIIT sprint type cardio on the treadmill for this winter and add weights to my work outs? I have been doing very little…only some yoga and light jogging a couple days per week. I want to get this 10 lbs off. I am only 5 ft tall and ten extra pounds is a lot on me, it's visible, clothes don't fit as well, and I can't wear my wedding rings. I don't want to do hcg again, even though it's the only thing that worked to get the weight off. I'll read the Post Rx. I think my hormones are still out of balance, something is wrong. Otherwise, why would I gain with my cycle each month, 10 lbs in 4 months? Thanks Dr. K. You are helping so many people.

My IGF 1 Insulin Like Growth Factor has been low for a number of years. Given my numerous head injuries and a diagnosis of SIADH, my endocrinologist had me undergo a glucagon stimulation test. My peak GH level was 15.9 mg/mL (normal >3) and my peak cortisol level was 27/7 mcg/dL (normal >18).

My endocrinologist said there was nothing that can be done. It seems to me that while my pituitary is capable of producing GH it is not doing so. Am I correct in my thinking and, if so, is there anything I can do?

So assuming the person survives the hypercortisol state for a while, can this eventually lead to adrenal insufficiency along with the thyroid dysfunction? Then what? What can be done for such a person? Can the adrenals be recovered and the rest of the system restored without again causing high cortisol? What would be your approach?

The original high cortisol issue was very likely mostly due to stress. The current low cortisol is perhaps adrenal fatigue. Hypothyroid and T4 to (useful)T3 conversion impaired. Complex situation I imagine with no measurements until the 'crash' already happened. Trying to dig out of the hole. General ectomorph body type, but abdomen is the place extra fat goes easily, esp. with sugar intake.

What is your take on using T3 only protocols, (similar to Wilson's protocol) to lower RT3 caused by severe overtraining / intermittent fasting that has not recovered on its own? (been over 6 months with plentiful diet, regular meals and no training at all)

If one has low testosterone could the normalisation of thyroid and metabolism bring that up?

(Have had GNRH stim, ACTCH stim, scan of testes and pituitary – all fine. Adrenal Stress Index curve is normal apart from 4th reading before bed which dips out of range)

Cortisol high, leptin resistance and very high rt3. Which one we should treat? Should i take T3 medication for high rt3 or not required..If i can rectify leptin resistance, is that enough? Please suggest

Found your site from MDA and am currently starting the Primal Lifestyle way of eating. Reading your site I'm certain I am LR but not sure what to tackle first. I am 32, 100+lbs overweight, have infertility, HBP and recently had bloodwork work that really concerns me. I was hoping I could give you some of the results and get some direction as what to do first, what tests to ask my Dr. to run for more clarification and how I should approach eating/exercise.

Fasting Glucose:95, Total Chol:187, HDL:46, LDL:119, Trig:110 and CRP: 16.3. (The cardiac CRP has been high still at 6-7 the past two years but I don't know if this is the HS CRP test). A1C: 5.8%, Alkaline Phosphatase:128. This panel is part of a large battery my husband's company does each year. I know I have to do something I just don't know where to start. Is the Leptin Rx right for me with the high CRP and low HDL? I have a recumbent bike and elliptical trainer at home and have been trying to spend 30 min a day on the bike…should I continue that or do the more strenuous elliptical? Thank you so much for all your information and help on my path to wellness & healing.

I am an enthusiastic newbie and just listened to your interview on living la vida low carb. I have a feeling you may have answers that I have failed to get from the medical community for 20 years. I have nocturnal panic attacks, they only occur while I am asleep (seemingly moving from one phase into another). Klonopin resolves them, but years of being on that created a horrible addiction and I assume health problems too. I have always suspected a hormone connection and am convinced I have crazy high cortisol levels. Do you have any insight or thoughts about this autonomic misfire during my sleep which grows into full blown panic? Also, do you know of a place in So. Cal. with reasonable lab testing? I just called Holtorf and its $400 just to go inside the clinic, then I have to cover the lab tests after that. Oy. Thanks, you are awesome!

@brenda my bet is inflammation is the cause…..one of your cytokines is driving it and I bet its coming from your gut. Get yourself a metametrix GI fx test and get a HS cRP and vitamin D level…….i bet they are all messed up. You can assess your sleep issue with a DHEA level I bet its quite low too.

I cried when I read your response, I didn't understand any of it, but I just felt you were again right on the money. My labs showed Pregnenolone, MS 34 ng/dL , Cortisol 9.5 ug/dL , Dehydroepiandrosterone (DHEA) 212 ng/dL , Vitamin D, 25-Hydroxy 24.2 ng/mL <–you were so right! C-Reactive Protein 0.87 mg/L , Reverse T3 243 pg/mL So, am I leptin resistant? And, can I start supplementing DHEA, Pregnenolone, and taking prometrium? Also should I do anything about the cortisol? You are amazing and I told that to my doctor who was so indignant about even letting me get this lab work done. Thank you!

Dr Kruse. You rock. I was wondering if you had any advice about my low testosterone, which is around 190-200 total naturally, I am 5'6 and 29 years and hypogonadal since my about 24. Thyroid ultrasound, brain/hypothalamus MRI all clean. Been on androgel testosterone for years now. About 6-7g daily. I have gone from being 210lbs to 156lbs since 2010. +/- 5lbs for a year now. I have had the androgel throughout my weight loss. Any thoughts on how I can naturally build it up without the Rx? I read online that the exoginous hormones can skrew up the complex symphony of hormone balance. Thoughts on that description? I am eating lower carb and higher fat, mostly on than off for two years now. My doc says I have had the caddilac of tests and believes my T levels are because of my previous obesity no other clues as to cause. I have carb cravings an am very irritable without the medicine. My estrogen and cortisol levels are normal. However I have relatively undeveloped musculature and a bit of gynecomastia. I never feel like exercising. I went to an endo and he also had nothing additional to offer. Other comorbidities: ADHD, dyscalculia/trouble determining left and right when stressed, and very mild tourettes.

Thanks for taking the time to answer people's questions. I am still reading your past blog posts, so apologies if this is answered elsewhere, but I took the cortisol saliva test, and found out my cortisol levels are high at night.

I've always been a night owl with trouble getting to bed early and up early, but in the last year I've started waking with a start shortly after falling asleep, sometimes with my heart racing or with an irregular beat. And a couple of times I had what I guess would be considered panic attacks. I've since cut out caffeine and a doc recommended Seriflos (but that just kept me up). Had the heart checked and it was fine.

I've been trying paleo for the last few weeks and have been gluten/dairy free for years (had leaky gut issues in the past and was diagnosed with several food sensitivities, most of which have improved, though dairy sensitivity is still sky high). I'm a few days into your leptin reset and am hoping that will ultimately be the answer. I'm trying to get to bed earlier, though the cortisol issues make it tough to fall asleep, and when I wake up, sometimes it takes hours to get back to sleep. It does seem to be helping that I'm not having night time snacks now. I'm fairly fit overall but have always been a snacker and sugar addict, so trying to get over all that too. 😉

I'm wondering if you have any other supplements or eating tactics you'd suggest to help with the night-time high cortisol and sleeping. Thanks!

P.S. I was on 4, 8, and 9 up there before I got off the gluten and dairy. Not taking anything except a multivitamin, fish oil, and magnesium now.

@Lynn I like L-theanine, phosphotidyl choline and serine, high rise magnesium malate 800-1200 mgs, DHEA replacement based upon your labs, bioidentical progesterone replacement based upon your labs…….and melatonin based upon your labs. If your gut is bad…….then I think about 5-HTP to replenish serotonin. You need testing to conquer this. Sleep hacks are my favorite but they are toughies for patients because it requires their full attn and effort. I will tell you the two best hacks for insomnia that you can start now……as soon as the sun set make your house as dark as possible……after a few days you will notice how it works. the other thing I recommend is buying a clark that has the sounds of nature on it as you sit/lay down in the dark. It relaxes you to meditate. I do a lot of TM and it helps sleep huge. Look into the book called The Healing Codes and do the exercises in the dark. I did this precisely last night because I was not tired. I slept like a rock.

I recently got a full thyroid panel. Everything in normal range except for rT3. The ratio to free T3 is about 2.5. Salivary cortisol showed normal. Should I get my dr on board to use Cytomel to reduce the rT3?

I'm in the fifth week of the leptin reset. Cravings were gone right away. About 8 lbs down. But I'm cold a lot, especially cold hands and feet, and feel lethargic.

Thanks so much. Just today I got my thyroid autoimmune report, and it shows high on thyroid peroxidase, in other words Hashimotos. For a little more info, I'm a 67-yr-old woman, 5'7", 182 lbs, with celiac disease and some fibromyalgia. I've been testing my BG lately, and it is showing up high, around 100 upon arising. After eating a high-carb meal last week, it was 198! This is the only high-carb meal I have eaten this year. This is getting tricky, since if I low-carb and keep my BG down, my rT3 may go up. I am determined, and have loads of practice in dealing with dietary restrictions. Any ideas?

@Lynnet you need to buy The Paleo Answer by Loren Cordain, Primal Blueprint by Mark Sisson or The paleo Solution by Robb Wolf…….they will all tell you how to eat. After you got the fuels you come back here and read the Leptin Rx and the Leaky Gut Rx…….I will help you climb yourself out of your rut.

Dr Kruse, what's your opinion of the cortisol/testosterone ratio? is it a good marker to improve? What's the difference between the salivary and serum testosterone test? Would having both be better than just one or the other?

@Michael the ratio is good for over training or to tell you if there is an imbalance between your adrenal and sympathetic nervous system. I like the cortisol/DHEA levels better because it is more sensitive.

I am now officially confused. I finally managed to score a copy of Cordain's book in New Zealand and find he recommends 'limiting eggs' to no more than 6 per week, omitting all bacon, eating a lot of chicken and using small amounts of CO (but recommending extra virgin olive oil more!). Since following your blog, completing the Leptin RX and now doing the post-Leptin reset living, I'm feeling great but eating lots of eggs (and lots of fish/shellfish, beef, venison, pork,and offal) and using CO as pretty much my only fat (and at every meal). He's also recommending half my calories from fruits & veggies. I realise he is recommending a healthy diet, not a diet for someone trying to cure something/fix a problem, but I'm mostly that category now (about 15 more pounds to lose, need to get strong/fitter, but no health complaints). Is this a contradiction or am I missing something? (P.S. Can't wait to hear more about the RX re: cold & ice!)

Thanks Dr Kruse. Yes, I realise that. I'm in the POST Rx mode. But when I asked you about your hierarchy of protein, what you suggested you follow (Wild Fish>shellfish>offal>pastured eggs>wild game meats like Deer/elk Bison>grass fed skeletal muscle meat>Ostrich>pastured pork>cured grass fed meats>protein from fowl's) seems in contradiction with his general recommendations. Are you saying, then, that once all health issues are cleared, I should switch to following Cordain's recommendations (specifically, reducing eggs, eating only lean meat, and using all fats, including coconut oil, sparingly?)? Thanks.

Just saw your post on Provera. I was on this drug for 2 years for heavy bleeding, was taken off in Nov 2011 as am now menopausal and have no bleeding anymore. Is there anything extra I should be doing to get the leptin reset working better since taking this drug? I did well at first, within the first 14 days I had lost 11 pounds, today is my 41st day and have lost 15 in total. It seems I lose weight when I first start a different way of eating, such as WW or low carb, then went low carb omega 3 and am now on the leptin reset, each time lost a bit of weight then stalled, been going up and down the last 4 pounds for over 3 weeks now. Lost inches the first couple weeks as well, but none since, I see you've advised people to just stick with it and it will eventually come off. I will eat this way for life as I feel best when I eat this way, have no snacks and no cravings, but I really would like to see this weight leave me, I could easily lose an avg person in weight 😐 so I'm far from being optimal. Maybe I need to start counting my protein grams and keep them lower then I've been eating, usually average around 100 grams a day. I also take all of your suggested supplements. Thanks for all your information.

I read your 2/11/12 post and have already ordered the compression suit as well as some bitter melon. I tried what BenG suggested by putting ice packs between the scapulas/lower neck area, left them there for 10 minutes, then moved them down to my belly area, wasn't cold enough for that though, it's been an hour and my lower neck area is still cold. I'm one of those that can't take much in temp wise, go 1 degree in either direction and I feel it, so hopefully this won't do me in 🙂 Looking forward to seeing more of what you post about this part of the leptin reset protocol.

While I do not think I'm LR (my cortisol levels decrease as the day goes on and I'm not currently overweight), my RT3 levels are high. After being on synthroid for several years, a new doc just put me on Nature-throid.

Can you give me any insight on how you would treat patients with elevated RT3 that are LS? Will Nature-throid be better than the synthetic synthroid? Anything else I could use to better treat it?

How about tests you would suggest to determine the root cause for the elevated RT3? Thanks!

Thanks Jack. I've pretty much been doing that for awhile now anyway since I've been on the GAPS diet and for the most part that follows your diet plan. What do you think of taking the Nature-throid with elevated RT3? Any problems there? I'm gaining weight lately and wondering if it has something to do with the NT/

Maybe you can't say Doc, but I'm curious if you think there's any harm in dropping my Nature-throid while following the post leptin Rx protocol? My last labs had my FT3 level normal, but my RT3 high. Since I'm not LR, can following the post leptin Rx resolve that high RT3 without any thyroid replacement hormones?

You posted above that low ferritin can also cause RT3. I've been searching for answers to my high RT3 for over a year now with no resolution. I do know I have low ferritin (26.1).

What do you suggest to increase ferritin? I follow a paleo diet and eat liver 2-3 times a week. All my other iron labs are good and I'm hesitant to supplement iron since I've read gut pathogens can feed on it and I know I have gut issues that I've been working through for a year now too.

I am coming in really late on this and don't want to wade through fifty billion comments to see if it has been addressed already but–I have had problems with heavy periods. In fact I went through about a three-year bout where they were so bad I'd have to break out the literal rag bag on the first day or two and couldn't leave my home for fear of accidents.

I read something at the Weston A. Price Foundation website, in passing, about how vitamin A was important in reproductive health and how some people are poor converters of beta carotene. I was intrigued and decided to try it for myself, derived from fish liver oil.

Bingo. My periods are probably still a little bit on the heavy side but they are manageable, and this weird twingy cramp thing I used to get in my left lower abdomen the day before the flow would start is gone gone GONE, as long as I've taken vitamin A regularly enough in the previous month. I have since heard about women in developing countries being treated by charity clinics for menhorragia, and the treatment is vitamin A supplementation.

Not that I don't think hormones could be playing a role in this as well. I'm one of those unfortunate folks who could desperately use a leptin reset as you have outlined elsewhere. But a subclinical vitamin deficiency was definitely part of the problem for me. Also, given how many children are wearing glasses now and given the fact that urinary tract defects are the number one type of birth defects in the United States, AND that women are discouraged from seeking out animal sources of vitamin A and also discouraged from eating liver during our pregnancies–I think this will shape up to be another vitamin-related health care crisis.

Adrenaline moves up" My answer is this……….when adrenal is up (adrenalin is up) it means cortisol is up at the brain levels. This means your diurnal cortisol cycle is broken. You can check that. When this happens, it means your thyroid wont work at all no matter how much tinkering you do. If this persists long enough every other hormone in the chain drops……if it remains persistent still you may find a chronic reduction in all of them that destroys you. This is caused by a lowered chronic secretion form alpha MSH. When this happens your leptin receptor is just about shot. When you are faced with this set of circumstance which most in the modern world are……….your first goal should be to stop the chronic cortisol release from he brain. Why? Cortisol turns off thyroid and it turns off immunity, and it destroys sleep. your metabolic efficiency is best read by your DHEA level. This correlates to yoru sleep status……..if you cant sleep you cant heal a thing and it means cortisol is up. the longer cortisol is up the more diurnal pattern changes I expect. The brain rewires to chronicty. it means it learns this is our nw way. With chronicity or Hebbian learning comes more permanent changes…….chronic high cortisol cause low alpha MSH…….chronic low alpha MSH destroys gut VIP which destroys your ability to account for circadian cycles…….when this happens you face major disease and you deplete your stem cells and you become a statistic.

What is the key to life? First you must lower cortisol by regaining LS. Everything starts with LS function… …when LS is regained all hormone receptor binding affinity rises……..when this happens it means the hormone levels become less important because the actionable factors can trigger a positive result with a small amount of hormone present. How do we fine tune our receptor affinity………..making ourselves LS to the optimal degree. How do we do that………just keep following the blog.

The QUILT is based upon foundational principles of what guides us to optimal life. To remain on this road you need to constantly remind your self of what are these foundational principals. Maintain ultimate receptor binding affinity is at the core what the QUILT will teach you at every turn. All 30 levees lead to this one principle.

We need to be constantly reminded of the basics of life so we remain directed at our life's purpose. When we live by assumptions, too often and we forget its fundamental concepts. Stop living your life by assumptions. When you assume things about the basics of life and forget what they are,……errors in judgement follow. Become mindful to find time every day to reconnect with the fundamentals in your life.

I finally have a full set of labs, as far as it's possible to get them during pregnancy (now 22 weeks). I am really, really struggling to find a doctor willing to help me with starting medication during pregnancy. I finally found one, but I would appreciate hearing hear whether you think cortisol followed by increasing doses of dessicated thyroid would be warranted based on these labs (in addition to leptin-reset dietary changes and a paleo diet). I understand that you can't give medical advice online; I'm mostly trying to understand whether these meds make sense, or whether a T3-only medication would be better, and whether cortisol is necessary before a person begins to take thyroid.

–Currently there's up to .4 degree variation in my daily averaged temps, and they're mostly less than 98.6 despite pregnancy.

Cortisol 24-Hour Salivary

8 am – 4.92

noon – 1.48

4 pm – 1.92

8 pm – 1.16

midnight – 1.22

4 am – 1.99

DHEA

8 am – 2.0

8 pm – 2.1

midnight – 3.9

Na

mEq/L

[136-145]

136

K

mEq/L

[3.5-5.0]

3.7

Magnesium

mg/dL

[1.8-2.5]

2.0

Iron

mcg/dL

[45-135]

75

Iron Binding Capacity

mcg/dL

[250-400]

284

Percent Saturation

[20.0-55.0]

26.0

Ferritin

mg/mL

[20-175]

96

Folate

ng/mL

[6-18]

18

Vitamin B12

pg/mL

[250-1,150]

402

TSH

mIU/L

[0.35-5.50]

1.08

Reverse T3

pg/ml

90-350

244

Free T4

NG/DL

.61-1.24

.66

T3 Free

pg/mL

2.3-4.2

2.3

[This gives me a 9.4 T3/RT3 ratio according to the "Stop the Thyroid Madness" calculator.]

TPO AB

IU/mL

[<9.0]

<0.3 f

Microsomal Ab

[<1:100]

<1:100

Anti-Thyroglobulin Ab

[<1:10]

<1:10

Thank you for your consideration–I am desperate to figure out what to do with continuing symptoms and don't want to make things worse by taking the wrong medications.

Reading this again today, with a better brain, makes so much more ensue. The key variable I was really missing was adequate total cholesterol. Mine was in the toilet when I did my salivary cortisol testing. Cortisol looked normal, but I am pretty sure that this was skewed by the low choleterol #s.(Low DHEAand preg and sex steroids except E), high rT3, Some Betaine and LR later, the TCholesterol shot up nicely, and I think I need to reassess the status of both the thyroid and cortisol/adrenals–old data might not be as meaningful. Is this correct thinking here? Not that many have the low cholesterol issue on the MDA boards, but for those that did and corrected, things looked sunnier rather quickly. Thank you!!

@Lucy Low cholesterol is a bad problem. The real reason are these two……when our cholesterol levels drop below 200 we start not having enough LDL cholesterol to perform cell division perfectly all the time. Many physicians are unaware that the mitotic spindle in all mammals need cholesterol for cell division. When you do not have enough your mitotic spindle is not as efficient and it can lead to aneuploidy and chromosomal damage. I personally think this is how many of the genetic diseases we face today are affected by. More bad news…….when humans get aneuploidy and chromosomal damage it leads to cancer…….oncogenesis. Now immediately go and look at any statin trial and go see if people die of cancer more when they take statins……..They do. This was also found in the Framingham heart study. I wrote about it here. http://jackkruse.com/why-does-heart-disease-reall…

Second big issue…….all human hormones are made from LDL cholesterol LDL converts to pregnenolone to start the chain of control with T3 and vitamin A as co factors. If your LDL is low, your hormone panels fall……and disease follows. The brain controls its 20 trillion cells in our body using hormones……so if you do not have good hormone control your brain is driving your metabolism with any eye sight. Our profession is blind to these effects but our customers are not. When I draw their labs daily and predict their levels from just looking at their MRI's they are kind of shocked. They should not be shocked because this is how biology of humans work via an evolutionary paradigm.

Fascinating. My entire (extended) family is plagued with serious cancers at a young age, and fits into the clinical pattern of Li Fraumeni syndrome–deferctive P53 monitoring. In the paternal line of same family they drop like flies from massive MIs, and modern bypass grafting has kept this latest generation alive longer. VERY FASCINATING. So sad. Also explains a lot about my personal hx of recurrent very early pregnancy loss with a TC of 125-135. And my mom freezing in summer 100 degree heat with bad hashi's and very low T Chol. Ouch, glad I know this, was headed for more disaster as I aged. REIs really need to get on board before they pump people up with un-opposed estrogens and no other recs.

As someone with cortisol related health issue, I know that the assertion that saliva hormone testing is dead accurate is completely false. There are two reasons for this, and the experiences of thousands of pituitary/adrenal patients online bear this out… Hormonal derangements cycle; if you don’t test when excess is being produced, you don’t know it’s happening. Cycles can be rapid, hour to hour, or from 12 hours to 85 days long. Getting accurate testing is a total crap shoot in those with dysfunctional HPA axis functioning.

In addition, without knowing the level of your CBG, (cortisol binding globulin), you have no way of interpreting a negatiSome of the most florid cases of Cushing’s disease;, for example, will never, or only rarely produce high test results on saliva or urine due to high CBG (common), probably an adaptation to try and maintain homeostasis. High CBG will make serum testing the only feasible method.

In any case, neither is accurate nor reliable. I’ve begun to believe, in fact, that hormone testing without knowing what binding globulin levels are uninformative. That’s before we even consider how wildly variable hormone receptor function and sensitivity is in various genetic kindreds.

[…] but rather is a marker for inflammation or infection in the body.Â Dr. Kruse says as much in his Hormones 101 post: So anytime the body is stressed or inflamed, it up-regulates cholesterol production to make more […]

Just got of out the cold bath and trying to warm up. Looking at some of your older posts and came across this one and read it with interest because this is next area I want to work on. I’ve been Primal almost 2 yrs and I’m down to 7-8% BF and in general feeling pretty good. However, when I look at my labs I see some values good to great and others not so and I’m confused where to go next and hoping for a bit of advice.
My Lab Numbers
Chol 250
HDL 71
LDL 166 although they’re 148 using the Iran Eq.
Trigs 73
CRP 0.24
Vit D 69.7
Vit B12 1002
Folate 12.9
Homocysteine 10 This one seems very odd condsidering the High B12 number
TSH 2.47
Testosterone 297

Thanks for all the information here and given at Paleo fx. But I have a question now that I have had the opportunity to digest the information some. PregnenoloneÂ is an important hormone clearly, can you take a supplement (a pill) to replenish it and sort of things straight, or does that just put a bandaid on a realÂ pregnenoloneÂ steal problem?
Thanks!!

@Wendy it depends……sometimes the problem is not enough LDL conversion to pregnenolone by T3 or Vitamin A. Other times it can be depleted because one of the steroid pathways is using pregnenolone to make that steroid. If cortisol levels are chronically raised, for example, we can deplete pregnenolone.

@Jack, my partner just got results back and her rT3 is 401 and total t3 is 73. At any point would CT (or too much of it) and/or kero diet induce more stress and lead to higher rev T3? At any point would you add some carbs in and/or minimize exposure to cold or is a best to keep going LRx and CT as much as possible to change things favorably?

Hi Dr. Kruse. This is all so informative. I hope I can ask all that I would like to very quickly and hope that as busy as you are you may be able to answer. I am 50 yrs old. I’ve been very healthy most of my life. My family generally looks and feels 10 yrs younger than they are. Out of nowhere in August of 2010, I had an episode of AFIB. Never any health problems and had stellar stress tests in the prior yr. I spent 48 hours in the hospital, it took that long to reset via medication. They ran every possible test to find out the reason and found none. However, as a reslut of these tests, the endo came to my room, and told me I have Hashimoto’s Thyroiditis. I asked him to repeat it, because he said it very quickly. He would not, he said, “all you need to remember is underactive thyroid” and follow up with me in 3 mos.” I did. He looked at my labs, said you don’t have underactive thyroid, you just need to lose wieght. (I’m about 50lbs overweight)I said well what about my low libido, losing my hair, trouble sleeping, depression,fatigue, sensitivity to cold? His response, “you just need to lose weight.” What about the diagnosis you gave me in the hospital? “I didn’t say that. You just need to lose weight” I could have argued and brought my discharge papers, but I was so angry, I never wanted to see or speak to him ever again. I found a Natural Medicine Doc, they did labs, told me I am on the verge of Thyroid disease, but it’s not close enough to treat(yet). However they did find a severe vitamin “D” deficiency and treate dit with prescription strength D. Also prescribed estrogen cream. I used it but never refilled. (long story why not) Nothing to do with faith in the treatment. I am wondering if you know of anyone in the Chicago area that treats with your methods in mind? Also I had a extremely stressful period in my life that lasted approx 14 yrs. Could being under high stress for all those years have triggered the events that lead to thyroid disese, D deficiency and can any or all of this relate to my lone bout with AFIB?

Dr. Kruse, can medications for Crohn’s disease/ulcerative colitis cause cortisol problems, in particular: prednisone, sulfa drugs, mercaptopurine? Just wondering if all the years I’ve taken these meds have done some more harm than good.

[…] X receptors (RXR), and RAR binds most of the forms of Vitamin A in our bodies. Remember from the Hormone 101 blog to make hormones we need Vitamin A and T3 to be present in good concentrations to convert LDL […]

Just getting into your site now and have always loved this information. In your experience have you seen mood/response changes for the better in those taking dietary measures to heal their LR? My boyfriend has recently started your dietary protocol and seems much more even keeled now, less likely to be reactive. I’d heard this once before in a friend who lessened/eliminated carbs. Thanks–and now I will dig in further to all this science and art–love it!

Trying to wrap my brain around all of this in light of some new labs and have some general questions about the relationships between these things . . .

Is it possible for pregnenalone steal syndrome and the turning off of the thyroid by CRH to happen even with a very low HS CRP (0.5)? Especially given the presence of altered cardiac metabolism,insulin resistance/PCOS, low T3, low T4, normal TSH, low pregnenalone, low DHEA, low 25 OH D, low estrogen, history of dysbiosis, history of circadian disruption, amenorrhea, and long-term stress . . . or would it have to be a different mechanism altogether in light of the low HS CRP?

Can the circadian disruption and gut dysbiosis in and of themselves cause leptin receptor signaling dysfunction and inflammation that leads to pregnenalone steal, decreased sex hormones, and thyroid shut off? If so, why doesn’t it show in the HS CRP? Is it that HS CRP is only going to be elevated if the inflammation came from elevated TNF?

Also, if the TSH is normal (1.8) and the T3 and T4 are low, is it a given that the reverse T3 (though untested) would be high, since the brain obviously isn’t increasing the TSH despite the low T4 and T3? . . . or is a reverse T3 level still necessary to determine the situation? Can we infer that CRH has turned off the thyroid if TSH is normal and T4 and T3 are both low? Could this be where a low ferritin could come in, or no because the T4 is also low?

@SCRN2007 Pregnenolone steal is a consequence not cause of the CRH and T3 link regardless of HS CRP level. Yes circadian biology of the gut when altered easily causes this. You are assuming a TSH of 1.8 is OK……..maybe it is not with that free T3 or free T4 level. To infer CRH is up we look at a 4 panel diurnal cortisol……I like it with an ASI best.

[…] also allows for even higher cortisol levels to develop quickly. Remember what I told you in the Hormone 101 blog post about high cortisol levels? A high cortisol level can not be sustained forever and eventually […]

@Jack so I re=read the H101 post. I read it to say high stress causes HIGH CORTISOL which, due to pregnenolone steal, causes decreased T3, sex hormones, sarcopenia and osteopenia.
But you said my cortisol was LOW..and you wanted it higher
So low cortisol could be a symptom also of pregnenelone steal – right? And increasing T3 and vit D is the key to making more pregnenelone and other hormones as well – right?

@Mitch when the effect is CHRONIC the decision in the cell is always on…..meaning all the pregnenolone shunts to cortisol to hep you survive. When we measure it in the plasma it is low…..that is a sign the PVN nucelus is working over time and this is sign your oxidizing your cells. The result is all the hormones going the other way in the hormone synthesis chain are very low……..that is the reduction path. Re Read BG 11. Low cortisol= low melatonin = epithelial cancers= LR. Oxidation =LR. Low cortisol is not a good thing. When the process first begins……ACUTELY you will have hyper cortisolism for a time until you fatigue your PVN nucleus output chemicals in the hypothalamus. Do it long enough and you oxidizes (age) your body, your sleep declines and your body fails with your body composition.

The critical equation of life = LDL + T3 = pregnenolone. If free T3 is low you cant make pregnenolone. If you live a life in the modern world you are in survival mode (living in the cortisol pathway of oxidation) shunting the already low amount of pregnenolone your cells can make to cortisol at the sake of making progesterone. Progesterone is the base hormone for the testosterone, estrogen, DHEA, etc (the hormones of fertility)……..The more we shunt to survival mode hormones the less fertility ones we make. More survival path activation of cortisol makes the cell more oxidized the faster the cell ages…….Moreover, the more oxidized the cell becomes the more Vitamin D has to be used to offset this increased oxidation by the immune system so Vitamin D levels also falls with oxidation. I hope this clarifies it. This is why modern humans are infertile (1 in 7 couples) because to have a child you must be more reduced than oxidized because it favors a higher level of the pro- GESTATION hormone called progesterone. Most modern humans are starved for progesterone because modern life keeps them in the survival pathway of cortisol. The cell always has to chose between survival or reproduction and inflammation is the traffic cop for the decision. Hence why we see upside down PG/E2 ratios in all modern neolithic diseases. when this happens the lab panel show increased HS CRP, increased E2, and LR, with LOW free T3 levels. Lowered Vitamin D levels are an epidemic because modern life forces us to live in a constant state of oxidation of the survival pathway (cortisol). I hope this answers it clearly now.

I suspect that you will find interesting the article below, which discusses the function of cortisol in the body as a hormone that inversely mobilizes the body against potassium wasting intestinal diseases, and in http://charles_w.tripod.com/cortisol.html with the references and links. If you see anything that can be improved please let me know. You may see a journal article that discusses this briefly in the 1998 vol. 51 issue of Medical Hypotheses, p 289-292.

It is proposed that the primary purpose of the glucocorticoids, including cortisol (hydrocortisone), is to mobilize the body to resist infection. They do so by normally altering processes which increase pathogens’ growth or their adverse effects and then declining when under attack. Cortisol is for intestinal disease (diarrhea) and corticosterone serum disease. Glucocorticoid mobilization for fight or flight is an adjunct, made possible because most processes which resist infection impair fight or flight. A different hormone controls those which do not.
Potassium loss is the most serious aspect of intestinal diseases, so the electrolyte capabilities of cortisol, but not corticosterone, are oriented toward conserving potassium. Low cell potassium reduces adrenal synthesis of cortisol, but not corticosterone. Sodium, water, glucose, amino acids, chloride, hydrogen ion, copper , and numerous others are controlled by cortisol in such a way as to survive during intestinal disease.
Some gram negative bacteria have an endotoxin which subverts this strategy by forcing the secretion of huge amounts of ACTH, which is the chief mediator of cortisol. A glucocorticoid response modifying factor (GRMF) and interleukin-1, raises the effective set point of cortisol. The immune cells thus take over their own regulation, using interleukin-1 to mediate production of cortisol via ACTH.
If you wish to see the whole article, please let meknow. No charge

I suspect that you will find interesting the article below, which discusses the function of cortisol in the body as a hormone that inversely mobilizes the body against potassium wasting intestinal diseases, and in http://charles_w.tripod.com/cortisol.html with the references and links. If you see anything that can be improved please let me know. You may see a journal article that discusses this briefly in the 1998 vol. 51 issue of Medical Hypotheses, p 289-292.
If you would like to see the rest of the article,send me an email.

I am interested in this. I have spent 2 hours reading this post and post from the people.

I am wondering what your opinion would be for me as well.

I was diagnosed after 5 years of asking my doctor over and over again to test me because of feeling bad and massive heartburn along with a large amount of weight gain. I had cervical cancer and received a partial hysterectomy last year and finally was able to get the blood test done.

I was put on levothyroxine and that it. I also take heartburn medication because I cannot stand myself when I get heartburn. I do know my triglycerides are sooo high..What would your advice be to establish a starting point to get my life back.

Trisha high TG = poor nnEMF environment, lack of UV light, and way too many carbs. Heart burn and cervical cancer are both signs of an environment that has allowed light mismatch to cause circadian disruption. Sounds like you are blue light toxic. Read the Ubiquitination series of blogs for more details.

I a bit late to this party but found your findings very interesting. There is allot of talk about the effects of high cortisol, high stress. What about once our cortisol has dropped and is completely low across the board. What can be done besides taking the dreaded hydrocortisone?

Amy 95% of people have low cortisol due to changes to our environment. I would suggest you read the Time series. Time 12 deals with this. An altered light spectrum disrupts the balance between the paraventricular nucleus (PVN) and the vagal systems that control the sympathetic tone versus the parasympathetic tone. Ubiquitination 24, Time 6, and Time 9 clearly show how UV light creates the correlated cycles of a controlled stressor and regeneration programs using the biogenic amines that control this entire process in the “eye clock” system. An altered spectrum of light via the eye camera mechanism can and does cause adrenal fatigue by lowering cortisol to extremely low levels. How?

Dopamine one of these biogenic amines controls release of most of the anterior pituitary hormones that act as proxies for clinicians to know when adrenal fatigue or PVN signaling is no longer optimized. We have known this since 1995. Endogenous hormone production is yoked directly to proper physiologic release of hormones using the solar spectrum. When the solar spectrum is altered at all, this alters the hormone panel that is measured by a lab. In this way, an altered hormone panel tells the astute clinician that the patient’s light environment is not full spectrum.

I was wondering if you could help me figure out what all my other docs have been unable to solve.

Basically, after being a life long heavy consumer of caffeine I had to stop due to it giving me hear palpitations and digestive problems.

Immediately after quitting cold turkey I had the normal withdrawal symptoms and they were severe! But, the worst part of this is that I started having horrible panic attacks with all the symptoms one could possibly have. I have never had these issues until quitting the caffeine. All my docs can tell me is that the caffeine was self medicating me but they can’t tell me how, they just say take this pill 🙁

Caffeine increases electron flow to spin the ATPase. Read Time 16 soon. When you abruptly stop it you slow the spinning of the ATPase. How can you gain back the speed without it or food? UV and IR light from the sun.

AM sunlight from the sunrise until UV shows up for your location is key

Shane
June 24, 2016 at 9:58 pm

Great! Thanks!

I recently got my schedule changed so I could get more AM sunlight. I eat my BF out on the porch as the sun comes up and then go for a light walk and do some mobility exercises out in the yard. I also try to get a little of the late afternoon light when I get home.

I live in in the middle GA area. I have also been walking outside at my 10 and 3 breaks but the UV is high at that point, maybe I should skip that and just do some mobility work inside?

Thank you so much for your time and all you do to get this knowledge out there for people!

Your last two sentences made me LOL. I wish my doctor would read this and feel like an idiot. He had me get blood work at 9am only and from that result told me that my adrenals were fine. I had a saliva test done that showed I had extremely low cortisol all day. He dismissed those results and sent me on my way.

I came across this because of a scary lab report today. I’m trying to research and learn. Also, I have t found any helpful doctors on this issue. My LDL is 132, but small particle, HDL is low at 4667. More concerning is my HS CRP is 31.8!! I’ve been told I have arthritis and Lyme but no symptoms now. I have been on birth control, but not during this lab test. I’ve looked multiple times and this is the number on my lab result. I went in to check thyroid. Those are out of range but not alarming. Total T4 12.6 above lab range of 4.5-12.0. Free T3 is only low baseline at 2.3. Always told I’m within normal range, not alarming or clinical hypo. Glucose is always good, between 72-84. Never told I was prediabetic.

I am obese. 44, 5’3-1/2″ and 213. I’m losing slowly on Ketogenic diet. Total lost in a month-1/2 is 15 pounds, but I’m stuck up and down 4 pounds the last 2 weeks. Then I came across your article! Can you help direct me? Any contacts or advise? I’m in the St. Louis, MO area. Like I said, I’m doing low carb, high fat, medium protein diet. I’m afraid a regular dr. Won’t know all this and put me on low fat!

You be wise to Read Kevin Cottrell exact journey in my CT series of blogs. He had a high HS CRP and dropped it in 30 days. You need a high protein moderate fat diet and low carb diet. Most likely your CRP is high due to the obesity and poor solar exposure you have in St. Louis.

Hi
If I have a BMI of 34 (20kg over weight) I have recently had my leptin test done and it’s low (8, range for my BMI is 19-121) I do have a reverse T3 of 24, 24 being the top of the range .. do I have leptin resistance? Or am I an anomaly? I’m not on thyroid meds or anything else prescribed.

[…] why the liver redox potential and the amount of T3 in your body are linked. Remember from the Hormone 101 blog that free T3 levels in the thyroid which allows the LDL to convert to pregnenolone, DHEA, and […]

About Dr. Kruse

Dr. Jack Kruse is a respected neurosurgeon and CEO of Optimized Life, a health and wellness company dedicated to helping patients avoid the healthcare burdens we typically encounter as we age. He is a member of the American Association of Neurological Surgeons, the Congress of Neurologic Surgeons, and Age Management Medicine Group.